Power, Sex, Suicide

by Nick Lane

  Mankind has always looked to the stars, and wondered why we are here, whether we are alone in this universe. We ask why our world is alive with plants and animals, and what were the chances against it; where we came from, who our ancestors were, what our destiny holds in store. The answer to the question of life, the universe and everything is not 42, as Douglas Adams once had it, but an almost equally cryptic shorthand: it is mitochondria. For mitochondria teach us how molecules sprang to life on our planet, and why bacteria dominated for so long. They show us why bacterial sludge is likely to be the climax of evolution across this lonely universe. They teach us how the first genuinely complex cells came into being, and why, since then, life on Earth has ascended a ramp of complexity to the glories we see around us, the great chain of being. They show us why energy-burning, warm-blooded creatures arose, thrusting off the shackles of the environment; why we have sex, two sexes, children, why we must fall in love. And they show us why our days in this firmament are numbered, why we must finally grow old and die. They show us, too, how we might better our twilight years, to stave off the misery of old age that curses humanity. If they don’t show us the meaning of life, they do at least make some sense of its shape. And what is meaning in this world, if it doesn’t make sense?

  Glossary

  Antioxidant any compound that protects against biological oxidation, either directly by becoming sacrificially oxidised itself in place of other molecules, or indirectly by catalysing the decomposition of biological oxidants.

  Apoptosis programmed cell death, or cell suicide; a finely orchestrated and carefully controlled mechanism for removing damaged or unnecessary cells from a multicellular organism.

  Archaea one of the three great domains of life, the other two being the eukaryotes and the bacteria; the archaea are similar to bacteria in their appearance down the microscope, but share a number of molecular similarities with the more complex eukaryotic cells.

  Archezoa a disparate group of single-celled eukaryotic organisms that lack mitochondria; at least some were originally thought never to have had any mitochondria at all, but now all are believed to have possessed mitochondria in their past, and later lost them.

  Asexual reproduction replication of a cell or organism, in which an exact clone of the parent cell or organism is produced.

  ADP adenosine diphosphate, the precursor of ATP.

  ATP adenosine triphosphate; the universal energy currency of life, which is formed from ADP (adenosine diphosphate) and phosphate; splitting ATP releases energy used to power many different types of biochemical work, from muscular contraction to protein synthesis.

  ATPase the enzyme motor within mitochondria that harnesses the flow of protons to form ATP from ADP and phosphate. ATPase is also known as ATP synthase.

  Cell the smallest biological unit capable of independent life, by means of self-replication and metabolism.

  Cell wall the tough but permeable outer ‘shell’ of bacterial, archaeal and some eukaryotic cells; maintains cell shape and integrity despite changes in physical conditions.

  Chemiosmosis the generation of a proton gradient across an impermeable membrane; the backflow of protons through special channels (the ATPase complexes) is used to power ATP formation.

  Chemiosmotic coupling the coupling of respiration to ATP synthesis by means of a proton gradient across a membrane; the energy released by oxidation is used to pump protons across a membrane, and the passage of protons back through the drive-shaft of the ATPase is used to power ATP synthesis.

  Chloroplast plant cell organelle responsible for photosynthesis; originally derived from endosymbiotic cyanobacteria.

  Chromosome long molecule of DNA, often wrapped in proteins such as histones; may be circular, as in bacteria and mitochondria, or straight, as in the nucleus of eukaryotic cells.

  Clonal replication alternative name for asexual reproduction.

  Control region stretch of non-coding DNA in the mitochondrial genome that binds factors responsible for controlling the expression of mitochondrial genes.

  Cytochrome c mitochondrial protein that shuttles electrons from complex III to complex IV of the respiratory chain; when released from the mitochondria, cytochrome c is a key initiator of apoptosis, or programmed cell death.

  Cytochrome oxidase functional name for complex IV of the respiratory chain: a multi-subunit enzyme that receives electrons from cytochrome c and uses them to reduce oxygen to water, the final step of cellular respiration.

  Cytoplasm the substance of the cell contained within the cell membrane, but excluding the nucleus.

  Cytoskeleton network of protein fibres within the cell that provides structural support; the structure is dynamic and enables some cells to change shape and move around.

  Cytosol the aqueous part of the cytoplasm, excluding organelles such as mitochondria and membrane systems.

  DNA deoxyribonucleic acid, the molecule responsible for heredity; it is composed of a double helix, in which nucleotide letters are paired with each other to form a template from which an exact copy of the whole molecule can be regenerated; the sequence of nucleotide letters encodes the sequence of amino acids in proteins.

  DNA sequence the sequence of nucleotide letters in DNA, which spells out the sequence of amino acids in proteins, or the binding sequences of transcription factors, or nothing at all.

  Electron tiny, negatively charged wave-particle that orbits the positively charged nucleus in atoms.

  Endosymbionts cells that live in a mutually beneficial relationship inside other cells.

  Endosymbiosis a mutually beneficial relationship in which one type of cell lives inside another larger cell.

  Enzyme a protein catalyst, responsible for speeding up biochemical reactions by many orders of magnitude, with enormous specificity.

  Eukaryote an organism, either single celled or multicellular, composed of eukaryotic cells

  Eukaryotic cell cells with a ‘true’ nucleus; all are thought to either possess, or have once possessed, mitochondria.

  Evolution rate the speed at which DNA sequence changes over many generations, which equates to the rate of mutations coupled to the purging effect of natural selection, which eliminates detrimental mutations, making the evolution rate slower than the mutation rate.

  Exponent a superscript number denoting the number of times a number should be multiplied by itself; the slope of a line on a log–log plot.

  Fermentation chemical splitting of sugars, without net oxidation or reduction, to form alcohol (or other substances); releases sufficient energy to synthesise ATP.

  Free radical an atom or a molecule with a single unpaired electron, which tends to be an unstable physical state leading to chemical reactivity.

  Free-radical leakage continuous low-level production of free radicals from the respiratory chains of the mitochondria, as a result of electron carriers reacting directly with oxygen.

  Gametes dedicated sex cells, such as sperm or eggs.

  Gene a stretch of DNA, whose sequence of nucleotide letters encodes a single protein.

  Genetic code the DNA letters, which encode the sequence of amino acids in proteins; particular combinations of letters specify particular amino acids, or other instructions such as ‘start’ and ‘stop’ reading.

  Genome the complete library of genes in an organism; the term is also taken to include non-coding (i.e. non-genic) stretches of DNA.

  Heteroplasmy a mixture of mitochondria (or other organelles) from two different sources, such as the father and the mother.

  Histones proteins that bind to DNA in a very particular structure, found only in eukaryotic cells and a few archaea, such as methanogens.

  Hydrogen hypothesis theory arguing that the eukaryotic cell originated as a chimera between two very different prokaryotic cells, in a metabolic symbiosis.

  Hydrogenosome organelle found in some anaerobic eukaryotic cells, which generates energy by fermenting organic fuels to release hydrogen gas; now known to have a common ance
stor with mitochondria.

  Lateral gene transfer the random transfer of segments of DNA, containing genes, from one cell to another, as opposed to vertical inheritance from mother to daughter.

  Lipid a type of long-chain fatty molecule found in biological membranes and as stored fuel.

  Membrane the thin fatty (lipid) layer that envelops cells, and forms complex systems inside eukaryotic cells.

  Metabolic rate the rate of energy consumption, measured by the rate of glucose oxidation or oxygen consumption in cells and whole organisms.

  Mitochondrial organelles within cells responsible for ATP generation, and for controlling cell suicide; derived from endosymbiotic α-proteobacteria, but exactly which is still disputed.

  Mitochondrial Eve the last common female ancestor of all humans living today, if judged by the slow divergence of mitochondrial DNA inherited asexually down the maternal line.

  Mitochondrial DNA the chromosome found in mitochondria, typically in five to ten copies, which is usually circular, and bacterial in nature.

  Mitochondrial genes the contingent of genes encoded by mitochondrial DNA; in humans there are 13 protein-coding genes, as well as genes encoding the RNA needed to manufacture proteins on site.

  Mitochondrial mutation an inherited alteration in the sequence of mitochondrial DNA.

  Mitochondrial disease a disease caused by mutations or deletions in mitochondrial DNA, or in nuclear genes encoding proteins targeted to the mitochondria.

  Mutation an inherited alteration in the sequence of DNA, which may have a negative, positive or neutral effect on function; natural selection, acting differentially on mutations in DNA, hones the function of proteins to specific tasks.

  Mutation rate the number of mutations occurring in DNA per unit time, usually a limited time period of a few generations; see also evolution rate.

  NADH nicotinamide adenine dinucleotide; a molecule that carries the electrons and protons ultimately derived from glucose to complex I of the respiratory chain, for use in respiration.

  Natural selection the differential survival and reproduction of individuals in a population, the members of which have heritable differences in biological fitness.

  Non-coding (junk) DNA sequences of DNA that do not encode proteins or RNA.

  Nucleus spherical membrane-enclosed ‘control centre’ of eukaryotic cells, containing chromosomes composed of DNA and protein.

  Oocyte egg cell; the female sex cell, containing half the number of chromosomes as a somatic (body) cell.

  Organelles tiny organs within cells dedicated to specific tasks, such as mitochondria and chloroplasts.

  Oxidation loss of electrons from an atom or molecule.

  Phagocytosis physical engulfment of particles by a cell, by means of changing shape and extending pseudopodia; the particles are digested in a food vacuole inside the cell.

  Prokaryote a broad class of single-celled organisms that do not possess a nucleus, including both bacteria and archaea.

  Protein a string of amino acids linked together in a chain, to form an almost infinite number of possible shapes and functions. Proteins form essentially all the machinery of life, including enzymes, structural fibres, transcription factors, DNA-binding proteins, hormones, receptors, and antibodies.

  Proton the nucleus of a hydrogen atom, with a single positive charge.

  Proton gradient a difference in proton concentration between one side of a membrane and the other.

  Proton leak the drizzle of protons back through a membrane that is nearly, but not quite, impermeable to protons.

  Proton pumping the physical translocation of protons from one side of a membrane to the other.

  Proton-motive force the potential energy stored in a proton gradient from one side of a membrane to the other; the combination of an electrical potential difference and the pH (proton concentration) difference.

  Recombination the physical crossing over and replacement of a gene from one source with the equivalent gene from another source; takes place in sexual reproduction and lateral gene transfer, and to repair a damaged chromosome by reference to a spare copy.

  Redox reaction a reaction in which one molecule is oxidized at the expense of another, which is accordingly reduced.

  Redox signalling the change in activity of a transcription factor as a result of its oxidation or reduction, usually by free radicals; the active transcription factor controls the expression of genes to form new proteins.

  Reduction gain of electrons by an atom or molecule.

  Reduction state the overall proportion of a population of molecules in the reduced state, as opposed to the oxidized state; if complex I is 70 per cent reduced, then 70 per cent of the complexes are in possession of respiratory electrons (they are reduced) and 30 per cent are oxidized.

  Respiration oxidation of foodstuffs to generate energy in the form of ATP.

  Respiratory chain the series of multi-subunit protein complexes embedded in the bacterial and mitochondrial membranes that pass electrons derived from glucose from one to the next, finally to react with oxygen in complex IV. The energy released by the passage of electrons is used to pump protons across the membrane.

  RNA ribonucleic acid; several forms exist, including messenger RNA (an exact copy of the DNA sequence in an individual gene, which translocates to the cytoplasm); ribosomal RNA (which forms part of the ribosomes, the protein-building factories found in the cytoplasm); and transfer RNA (an adapter that couples a nucleotide code to a particular amino acid).

  Sexual reproduction reproduction by means of the fusion of two sex cells, or gametes, each of which contains a random assortment of half the parental genes, to give an embryo with an equal number of genes from both parents.

  Symbiosis a mutually beneficial relationship between organisms of two different species.

  Transcription factor a protein that binds to a DNA sequence, to signal the transcription of a gene into an RNA copy, as the first step of protein synthesis.

  Uncoupling dissociation of respiration from ATP production; instead of the proton gradient powering ATP synthesis through the ATPase, protons pass back through membrane pores, dissipating the gradient as heat; uncoupling the respiratory chain is equivalent to uncoupling a bicycle chain, thereby disconnecting peddling from forward momentum.

  Uncoupling protein a protein channel in the membrane that enables the passage of protons back through the membrane, dissipating the proton gradient as heat.

  Uncoupling agent any chemical that dissipates the proton gradient by shuttling protons across the membrane, thereby dissociating respiration from ATP production.

  Uniparental inheritance the inheritance of mitochondria (or chloroplasts) from only one of two parents, specifically the mother.

  Further Reading

  Introduction

  General texts

  Fruton, J. Proteins, Enzymes, Genes: The Interplay of Chemistry and Biology. Yale University Press, New Haven, USA, 1999.

  Margulis, Lynn. Origin of Eukaryotic Cells. Yale University Press, Yale, USA, 1970.

  —— Gaia is a tough bitch. In John Brockman (ed.), The Third Culture: Beyond the Scientific Revolution. Simon & Schuster, New York, USA, 1995.

  Sapp, Jan. Evolution by Association: A History of Symbiosis. Oxford University Press, Oxford, UK, 1994.

  Wallin, Ivan. Symbionticism and the Origin of Species. Bailliere, Tindall and Cox, London, UK, 1927.

  The nature of mitochondria

  Attardi, G. The elucidation of the human mitochondrial genome: A historical perspective. Bioessays 5: 34–39; 1986.

  Baldauf, S. L. The deep roots of eukaryotes. Science 300: 1703–1706; 2003.

  Cooper, C. The return of the mitochondrion. The Biochemist 27(3): 5–6; 2005.

  Dyall, S. D., Brown, M. T., and Johnson, P. J. Ancient invasions: From endosymbionts to organelles. Science 304: 253–257; 2004.

  Griparic, L., and van der Bliek, A. M. The many shapes of mitochondrial membranes. Traffic 2: 235–244; 20
01.

  Kiberstis, P. A. Mitochondria make a comeback. Science 283: 1475; 1999.